Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cells can read damaged DNA without missing a beat

10.02.2010
Scientists have shown that cells' DNA-reading machinery can skim through certain kinds of damaged DNA without skipping any letters in the genetic "text." The studies, performed in bacteria, suggest a new mechanism that can allow bacteria to develop resistance to antibiotics.

The results were published online this week in the Proceedings of the National Academy of Sciences. The senior author is Paul Doetsch, PhD, professor of biochemistry and radiation oncology at Emory University School of Medicine and associate director for basic research at Winship Cancer Institute of Emory University.

Working with Doetsch, graduate student Cheryl Clauson examined the ability of RNA polymerase (the enzyme that transcribes, or makes RNA from DNA) to handle damaged DNA templates.

RNA polymerase reads one strand of the double helix and assembles RNA that is complementary to that strand. In test tube experiments, when the enzyme comes to a gap or a blank space, it keeps reading but leaves out letters across from the damaged stretch. In contrast, in cells, RNA polymerase puts a random letter (preferring A) across from the gap.

"We were surprised to find that the transcription machinery rolls right over the damaged portion," Doetsch says. "This shows that if the cell initiates, but doesn't complete repair, it still can lead to mutagenesis."

Clauson says a challenge in planning her experiments was finding a way to sensitively detect when RNA polymerase reads through DNA damage.

She loaded damaged DNA into a gene that encodes an enzyme from fireflies, which generates light-emitting chemicals, and then introduced that gene into bacteria. A full working enzyme is produced only if RNA polymerase bypasses the DNA damage without skipping any letters.

DNA in every type of cell, whether bacterial, plant or animal, is constantly being damaged by heat, oxygen and radiation. In addition, all cells make RNA from some of their genes to produce proteins and carry out their normal functions. Cells periodically copy their DNA before dividing, but only if conditions are right for them to grow.

The experiments were performed in bacteria with mutations disabling some forms of DNA repair, Clauson says.

"This situation may resemble one where something like radiation or a mutagenic chemical has overwhelmed the normal repair mechanisms," she says.

In addition, Clauson used an antibiotic called novobiocin to shut down DNA replication in the bacteria. She says this simulates a more challenging environment when cells are not growing quickly.

"Our ability to see transcriptional mutagenesis in growth-limiting conditions is important," Doetsch says. "Out in the environment, bacteria are not constantly surrounded by the rich mix of nutrients we give them in the lab."

"Because this work hints at a simple mechanism by which bacteria could escape from growth-restricted environments, it has important implications for how pathogenic microorganisms may acquire resistance to antibiotics," he adds. The next phase of these studies for Doetsch and colleagues will be to test whether transcriptional mutagenesis can lead directly to antibiotic resistance in bacteria and other microorganisms.

The research was supported by the National Institutes of Health.

Reference:

C.L. Clauson, K.J. Oestreich, J.W. Austin and P.W. Doetsch. Abasic sites and strand breaks in DNA cause transcriptional mutagenesis in Escherichia coli. PNAS Early Edition (2010)

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has $2.3 billion in operating expenses, 18,000 employees, 2,500 full-time and 1,500 affiliated faculty, 4,500 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

Learn more about Emory's health sciences: http://emoryhealthblog.com - @emoryhealthsci (Twitter) - http://emoryhealthsciences.org

Vince Dollard | EurekAlert!
Further information:
http://emoryhealthsciences.org

More articles from Life Sciences:

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

nachricht Inactivate vaccines faster and more effectively using electron beams
23.03.2017 | Fraunhofer-Institut für Organische Elektronik, Elektronenstrahl- und Plasmatechnik FEP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Inactivate vaccines faster and more effectively using electron beams

23.03.2017 | Life Sciences

New study maps space dust in 3-D

23.03.2017 | Physics and Astronomy

Tracing aromatic molecules in the early universe

23.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>